Article

Meta-analysis of the association between the 7-repeat allele of the dopamine D-4 receptor gene and attention deficit hyperactivity disorder

Harvard University, Cambridge, Massachusetts, United States
American Journal of Psychiatry (Impact Factor: 13.56). 08/2001; 158(7):1052-7. DOI: 10.1176/appi.ajp.158.7.1052
Source: PubMed

ABSTRACT Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-repeat allele of the dopamine D(4) receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain.
Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias.
For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias.
Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nearby gene) accounts for this association.

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    ABSTRACT: A B S T R A C T The dopamine D4 receptor (DRD4) is the most important gene in psychiatric genetics since its involvement in the physiology of behavior, pharmacology response and psychopathology. DRD4's sequence gene present some polymorphism such as in the exon 3 constituted from 2 to 10 copies of repetitive se-quences of 48 base pair (bp), from class variable number tan-dem repeats (VNTR). An additional genetic variant in the exon 1 presents polymorphisms to 12 bp VNTR, and the va-riation -521 C by T of the promoter region. The –521 T allele can reduce the efficiency of the gene expression in comparison with the C allele. The DRD4 gene codes a protein transmem-branal of 7 domains, distributed in front cortex, striatum, hypothalamus and hippocampus. This review discusses the biological significance of DRD4 gene and its perspective with emphasis on the impact of association studies in some illness mental and behavioral traits. The DRD4 polymorphism has been studied in association with illnesses like schizophrenia, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive with tics, bipolar manic-depressive disorder, in addition behavioral traits such as novelty seeking. The DRD4 gene is a genetic marker that could play a role in etiology of di-fferent mental illness, and behavioral traits, and its polymor-phism can be used in association studies, epigenetic and phar-macogenomic analysis for help to understand the genetics basis of both mental disorders and traits. RESUMEN El gen receptor a dopamina D4 (DRD4) ha sido analizado por su estructura, su polimorfismo genético, su constitución pro-teínica, su distribución neuroanatómica y su respuesta far-macológica. La secuencia del gen DRD4 presenta varios poli-morfismos, como del tipo número variable de repetidos en tándem (VNTR) en el exón 3, el VNTR de 12 pares de bases del exón 1 y el polimorfismo único de nucleótidos (SNP) de la región del promotor. El gen DRD4 codifica una proteína transmembranal de 7 dominios, que se distribuye en corteza frontal, en estriado, en hipotálamo y en el hipocampo. Esta re-visión discute la importancia biológica del gen DRD4 y sus perspectivas ante nuevas áreas de investigación con énfasis en recientes estudios de asociación en diferentes enfermedades mentales y en comportamientos. El DRD4 es uno de los genes candidatos cuya variación polimórfica ha sido relacionada con algunos trastornos psiquiátricos como esquizofrenia, trastor-no de déficit de atención e hiperactividad, obsesivo compulsivo con tics y trastorno por consumo de sustancias, así como con la característica de personalidad de búsqueda de la novedad. El gen DRD4 es un marcador genético y un modelo útil para es-tudios de asociación, epigenéticos y farmacogenómicos que buscan identificar el origen de trastornos psiquiátricos y com-portamientos.
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    Handbook of biosocial criminology, Edited by Matt DeLisi, Matthew G. Vaughn, 01/2015: pages 101-114; Routledge.

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